Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Pantoprazole Sodium for Injection is supplied in a single-dose vial as a white to off-white sterile lyophilized powder for reconstitution containing 40 mg of pantoprazole. Pantoprazole Sodium for Injection is available as follows: NDC Number S trength P ac kage Size 0143-9284-10 40 mg pantoprazole 10 vials S torage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light.; PRINCIPAL DISPLAY PANEL NDC 0143- 9284 -01 Rx only Pantoprazole Sodium for Injection Equivalent to pantoprazole 40 mg per vial Sterile For Intravenous Infusion ONLY Single Dose Vial Discard unused portion NDC 0143- 9284 -10 Rx only Pantoprazole Sodium for Injection Equivalent to pantoprazole 40 mg per vial Sterile For Intravenous Infusion ONLY Single Dose Vial Discard unused portion No filter required Contains 10 Vials PLB093-WES,2 PLB094-WES.2; SERIALIZATION IMAGE Representative Carton Serialization Image Representative Carton Serialization Image
- 16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Pantoprazole Sodium for Injection is supplied in a single-dose vial as a white to off-white sterile lyophilized powder for reconstitution containing 40 mg of pantoprazole. Pantoprazole Sodium for Injection is available as follows: NDC Number S trength P ac kage Size 0143-9284-10 40 mg pantoprazole 10 vials S torage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light.
- PRINCIPAL DISPLAY PANEL NDC 0143- 9284 -01 Rx only Pantoprazole Sodium for Injection Equivalent to pantoprazole 40 mg per vial Sterile For Intravenous Infusion ONLY Single Dose Vial Discard unused portion NDC 0143- 9284 -10 Rx only Pantoprazole Sodium for Injection Equivalent to pantoprazole 40 mg per vial Sterile For Intravenous Infusion ONLY Single Dose Vial Discard unused portion No filter required Contains 10 Vials PLB093-WES,2 PLB094-WES.2
- SERIALIZATION IMAGE Representative Carton Serialization Image Representative Carton Serialization Image
Overview
The active ingredient in Pantoprazole Sodium for Injection, a PPI, is a substituted benzimidazole, sodium 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridyl)methyl]sulfinyl]-1 H -benzimidazole sesquihydrate, a compound that inhibits gastric acid secretion. Its empirical formula is C 16 H 14 F 2 N 3 NaO 4 S•1.5 H 2 O, with a molecular weight of 432.37. The structural formula is: Pantoprazole sodium is a white to off-white crystalline powder and is racemic. Pantoprazole sodium is freely soluble in water, very slightly soluble in phosphate buffer at pH 7.4, and practically insoluble in n-hexane. The stability of the compound in aqueous solution is pH-dependent. The rate of degradation increases with decreasing pH. The reconstituted solution of Pantoprazole Sodium for Injection is in the pH range 9.5 to 11.5. Pantoprazole Sodium for Injection is supplied for intravenous administration as a sterile lyophilized powder in a single-dose clear glass vial fitted with a rubber stopper and crimp seal. Each vial contains 40 mg pantoprazole (equivalent to 45.1 mg of pantoprazole sodium), and sodium hydroxide to adjust pH. structure
Indications & Usage
Pantoprazole Sodium for Injection is a proton pump inhibitor (PPI) indicated in adults for the following: • Short-term treatment (7 to 10 days) of gastroesophageal reflux disease (GERD) associated with a history of erosive esophagitis (EE). ( 1.1 ) • Pathological hypersecretion conditions, including Zollinger-Ellison (ZE) syndrome. ( 1.2 ) 1.1 Gastroesophageal Reflux Disease Associated with a History of Erosive Esophagitis Pantoprazole Sodium for Injection is indicated for short-term treatment (7 to 10 days) of adult patients with gastroesophageal reflux disease (GERD) and a history of erosive esophagitis (EE). Safety and efficacy of Pantoprazole Sodium for Injection as a treatment of patients with GERD and a history of EE for more than 10 days have not been demonstrated. 1.2 Pathological Hypersecretion Including Zollinger-Ellison Syndrome Pantoprazole Sodium for Injection is indicated for the treatment of pathological hypersecretory conditions including Zollinger-Ellison (ZE) Syndrome in adults.
Dosage & Administration
G ERD Associated with EE ( 2.1 ) : • The recommended adult dosage is 40 mg administered once daily by intravenous infusion for 7 to 10 days. P ath olog ica l Hypersecretory Conditions, Including ZE Syndrome ( 2.3 ): • The recommended adult dosage is 80 mg administered every 12 hours by intravenous infusion. See the full prescribing information for information on how to adjust dosing for individual patient needs. A d ministration ( 2.2 , 2.4 ) : • Only for intravenous infusion. • The intravenous infusion can be administered over 2 minutes or 15 minutes. • For information on how to prepare and administer for each indication, see the full prescribing information. 2.1 Dosage for Gastroesophageal Reflux Disease Associated With a History of Erosive Esophagitis The recommended adult dosage of Pantoprazole Sodium for Injection is 40 mg given once daily by intravenous infusion for 7 to 10 days. Discontinue treatment with Pantoprazole Sodium for Injection as soon as the patient is able to receive treatment with pantoprazole sodium delayed-release tablets or oral suspension. Data on the safe and effective dosing for conditions other than those described [see Indications and Usage (1) ] such as life-threatening upper gastrointestinal bleeds, are not available. Pantoprazole Sodium for Injection 40 mg once daily does not raise gastric pH to levels sufficient to contribute to the treatment of such life-threatening conditions. 2.2 Preparation and Administration Instructions for Gastroesophageal Reflux Disease Associated with a History of Erosive Esophagitis For intravenous infusion only. F ifteen Minute Infusion 1. Reconstitute Pantoprazole Sodium for Injection with 10 mL of 0.9% Sodium Chloride Injection, USP 2. Further dilute with 100 mL of 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, USP, or Lactated Ringer's Injection, USP, to a final concentration of approximately 0.4 mg/mL. 3. Inspect the diluted Pantoprazole Sodium for Injection solution visually for particulate matter and discoloration prior to and during administration. 4. Administer intravenously over a period of approximately 15 minutes at a rate of approximately 7 mL/minute. Storage The reconstituted solution may be stored for up to 6 hours at room temperature prior to further dilution. The diluted solution may be stored at room temperature and must be used within 24 hours from the time of initial reconstitution. Both the reconstituted solution and the diluted solution do not need to be protected from light. Do not freeze either the reconstituted or diluted solutions. Two Minute Infusion 1. Reconstitute Pantoprazole Sodium for Injection with 10 mL of 0.9% Sodium Chloride Injection, USP, to a final concentration of approximately 4 mg/mL. 2. Inspect the diluted Pantoprazole Sodium for Injection solution visually for particulate matter and discoloration prior to and during administration. 3. Administer intravenously over a period of at least 2 minutes. Storage The reconstituted solution may be stored for up to 24 hours at room temperature prior to intravenous infusion and does not need to be protected from light. Do not freeze either the reconstituted or diluted solutions. 2.3 Dosage for Pathological Hypersecretion Including Zollinger-Ellison Syndrome The recommended adult dosage of Pantoprazole Sodium for Injection is 80 mg intravenously every 12 hours. The frequency of dosing can be adjusted to individual patient needs based on acid output measurements. In those patients who need a higher dosage, 80 mg intravenously every 8 hours is expected to maintain acid output below 10 mEq/h. Daily doses higher than 240 mg or administered for more than 6 days have not been studied [see Clinical Studies (14.2) ] . Transition from oral to intravenous and from intravenous to oral formulations of gastric acid inhibitors should be performed in such a manner to ensure continuity of effect of suppression of acid secretion. Patients with ZE Syndrome may be vulnerable to serious clinical complications of increased acid production even after a short period of loss of effective inhibition. 2.4 Preparation and Administration Instructions for Pathological Hypersecretion Including Zollinger-Ellison Syndrome For intravenous infusion only. Fifteen Minute Infusion 1. Reconstitute each vial of Pantoprazole Sodium for Injection with 10 mL of 0.9% Sodium Chloride Injection, USP. 2. Combine the contents of the two vials and further dilute with 80 mL of 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, USP, or Lactated Ringer's Injection, USP, to a total volume of 100 mL with a final concentration of approximately 0.8 mg/mL. 3. Inspect the diluted Pantoprazole Sodium for Injection solution visually for particulate matter and discoloration prior to and during administration. 4. Administer intravenously over a period of approximately 15 minutes at a rate of approximately 7 mL/minute. Storage The reconstituted solution may be stored for up to 6 hours at room temperature prior to further dilution. The diluted solution may be stored at room temperature and must be used within 24 hours from the time of initial reconstitution. Both the reconstituted solution and the diluted solution do not need to be protected from light. Do not freeze either the reconstituted or diluted solutions. Two Minute Infusion 1. Reconstitute Pantoprazole Sodium for Injection with 10 mL of 0.9% Sodium Chloride Injection, USP, per vial to a final concentration of approximately 4 mg/mL. 2. Inspect the reconstituted Pantoprazole Sodium for Injection solution visually for particulate matter and discoloration prior to and during administration. 3. Administer the total volume from both vials intravenously over a period of at least 2 minutes. Storage The reconstituted solution may be stored for up to 24 hours at room temperature prior to intravenous infusion and does not need to be protected from light. Do not freeze the reconstituted solution. 2.5 Compatibility Information • Administer Pantoprazole Sodium for Injection intravenously through a dedicated line or through a Y-site. • Flush the intravenous line before and after administration of Pantoprazole Sodium for Injection with either 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, USP, or Lactated Ringer's Injection, USP. • When administered through a Y-site, Pantoprazole Sodium for Injection is compatible with the following solutions: 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, USP, or Lactated Ringer's Injection, USP. • Midazolam HCl has been shown to be incompatible with Y-site administration of Pantoprazole Sodium for Injection. • Pantoprazole Sodium for Injection may not be compatible with products containing zinc. • When administered through a Y-site, immediately discontinue the infusion if precipitation or discoloration occurs.
Warnings & Precautions
• Gastric Malignancy : In adults, symptomatic response to therapy with Pantoprazole Sodium for Injection does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing. ( 5.1 ) • Injection Site Reactions : Thrombophlebitis is associated with intravenous use. ( 5.2 ) • Acute Tubulointerstitial Nephritis : Discontinue treatment and evaluate patients. ( 5.3 ) • Clostridium difficile -Associated Diarrhea : PPI therapy may be associated with increased risk. ( 5.4 ) • Bone Fracture : Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. ( 5.5 ) • Severe Cutaneous Adverse Reactions : Discontinue at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. ( 5.6 ) • Cutaneous and Systemic Lupus Erythematosus : Mostly cutaneous; new onset or exacerbation of existing disease; discontinue Pantoprazole Sodium for Injection and refer to specialist for evaluation. ( 5.7 ) • Hepatic Effects : Elevations of transaminases observed. ( 5.8 ) • Hypomagnesemia and Mineral Metabolism : Reported rarely with prolonged treatment with PPIs. ( 5.9 ) • Fundic Gland Polyps : Risk increases with long-term use, especially beyond one year. Use the shortest duration of therapy. ( 5.10 ) 5.1 Presence of Gastric Malignancy In adults, symptomatic response to therapy with Pantoprazole Sodium for Injection does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. In older patients, also consider an endoscopy. 5.2 Injection Site Reactions Thrombophlebitis was associated with the administration of another intravenous pantoprazole sodium product. 5.3 Acute Tubulointerstitial Nephritis Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue Pantoprazole Sodium for Injection and evaluate patients with suspected acute TIN [see Contraindications (4) ] . 5.4 Clostridium difficile -Associated Diarrhea Published observational studies suggest that PPI therapy like Pantoprazole Sodium for Injection may be associated with an increased risk of Clostridium difficile- associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions (6.2) ]. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. 5.5 Bone Fracture Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration (2.2 , 2.4) and Adverse Reactions (6) ] . 5.6 Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs [see Adverse Reactions (6.2) ] . Discontinue Pantoprazole Sodium for Injection at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. 5.7 Cutaneous and Systemic Lupus Erythematosus Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including pantoprazole sodium. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematous cases were CLE. The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement. Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported. Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving Pantoprazole Sodium for Injection, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g. ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations. 5.8 Hepatic Effects Mild, transient transaminase elevations have been observed in clinical studies. The clinical significance of this finding in a large population of subjects administered intravenous pantoprazole sodium is unknown [see Adverse Reactions (6.1) ]. 5.9 Hypomagnesemia and Mineral Metabolism Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, and in most cases after a year of therapy. Serious adverse reactions include tetany, arrhythmias, and seizures. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), healthcare professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2) ]. Consider monitoring magnesium and calcium levels prior to initiation of Pantoprazole Sodium for Injection and periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism). Supplement with magnesium and/or calcium as necessary. If hypocalcemia is refractory to treatment, consider discontinuing the PPI. 5.10 Fundic Gland Polyps PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated. 5.11 Interference with Investigations for Neuroendocrine Tumors Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Healthcare providers should temporarily stop Pantoprazole Sodium for Injection treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary [see Clinical Pharmacology (12.2) ] . 5.12 Interference with Urine Screen for THC Pantoprazole sodium may produce a false-positive urine screen for THC (tetrahydrocannabinol) [see Drug Interactions (7) ]. 5.13 Concomitant Use of Pantoprazole Sodium for Injection with Methotrexate Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients [see Drug Interactions (7) ].
Contraindications
• Pantoprazole Sodium for Injection is contraindicated in patients with known hypersensitivity reactions including anaphylaxis to the formulation or any substituted benzimidazole. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see Warnings and Precautions (5.3) , Adverse Reactions (6) ] . • Proton pump inhibitors (PPIs), including Pantoprazole Sodium for Injection, are contraindicated in patients receiving rilpivirine-containing products [see Drug Interactions (7) ] . • Patients with known hypersensitivity to any component of the formulation or to substituted benzimidazoles. ( 4 ) • Patients receiving rilpivirine-containing products ( 4 , 7 )
Adverse Reactions
The following serious adverse reactions are described below and elsewhere in labeling: • Injection Site Reactions [see Warnings and Precautions (5.2) ] • Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.3) ] • C lostridium difficile- Associated Diarrhea [see Warnings and Precautions (5.4) ] • Bone Fracture [see Warnings and Precautions (5.5) ] • Severe Cutaneous Adverse Reactions [See Warnings and Precautions (5.6) ] • Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.7) ] • Hepatic Effects [see Warnings and Precautions (5.8) ] • Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions (5.9) ] • Fundic Gland Polyps [see Warnings and Precautions (5.10) ] Most common adverse reactions (>2%) are: headache, diarrhea, nausea, abdominal pain, vomiting, flatulence, dizziness, and arthralgia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of Pantoprazole Sodium for Injection has been established from adequate and well-controlled studies of another intravenous pantoprazole sodium product [see Clinical Studies (14) ] . Below is a display of the adverse reactions of pantoprazole sodium in these adequate and well-controlled studies. Gastroesophageal Reflux Disease (GERD) Safety in nine randomized comparative US clinical trials in patients with GERD included 1,473 patients on oral pantoprazole (20 mg or 40 mg), 299 patients on an H 2 -receptor antagonist, 46 patients on another PPI, and 82 patients on placebo. The most frequently occurring adverse reactions are listed in Table 1. The number of patients treated in comparative studies with intravenous pantoprazole sodium is limited; however, the adverse reactions seen were similar to those seen in the oral studies. Thrombophlebitis was the only new adverse reaction identified with intravenous pantoprazole sodium. T able 1: Adverse Reactions Reported in Clinical Trials of Adult Patients with GERD at a Frequency of >2% O ral Pantoprazole Sodium ( n=1473) % C o m parators ( n=345) % P lacebo ( n=82) % Headache 12.2 12.8 8.5 Diarrhea 8.8 9.6 4.9 Nausea 7 5.2 9.8 Abdominal pain 6.2 4.1 6.1 Vomiting 4.3 3.5 2.4 Flatulence 3.9 2.9 3.7 Dizziness 3 2.9 1.2 Arthralgia 2.8 1.4 1.2 Additional adverse reactions that were reported for oral pantoprazole sodium in US clinical trials with a frequency of 2% or less are listed below by body system: Body as a Whole: allergic reaction, fever, photosensitivity reaction, facial edema, thrombophlebitis (intravenous only) Gastrointestinal: constipation, dry mouth, hepatitis Hematologic: leukopenia (reported in ex-US clinical trials only), thrombocytopenia Me tabolic/Nutritional: elevated CPK (creatine phosphokinase), generalized edema, elevated triglycerides, liver function tests abnormal M usculoskeletal: myalgia N e rvous: depression, vertigo Skin and Appendages: urticaria, rash, pruritus Special Senses: blurred vision Z ollinger-Ellison Syndrome In clinical studies of Zollinger-Ellison Syndrome, adverse reactions reported in 35 patients administered oral pantoprazole doses of 80 mg to 240 mg per day for up to 2 years were similar to those reported in adult patients with GERD. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of other pantoprazole sodium products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These adverse reactions are listed below by body system: General Disorders and Administration Conditions: asthenia, fatigue, malaise I mmune System Disorders: anaphylaxis (including anaphylactic shock), systemic lupus erythematosus I nvestigations: weight changes Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions (some fatal), including erythema multiforme, SJS/TEN, DRESS, AGEP [see Warnings and Precautions (5.6) ] , and angioedema (Quincke's edema) and cutaneous lupus erythematosus Musculoskeletal Disorders: rhabdomyolysis, bone fracture Renal and Genitourinary Disorders: interstitial nephritis, erectile dysfunction Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure Psychiatric Disorder: hallucinations, confusion, insomnia, somnolence Metabolism and Nutritional Disorders: hypomagnesemia, hypocalcemia, hypokalemia [see Warnings and Precautions (5.9) ] , hyponatremia Infections and Infestations: Clostridium difficile- associated diarrhea Hematologic: pancytopenia, agranulocytosis N e rvous: ageusia, dysgeusia Gastrointestinal Disorders: fundic gland polyps
Drug Interactions
Table 2 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with Pantoprazole Sodium for Injection and instructions for preventing or managing them. Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs. T able 2: Clinically Relevant Interactions Affecting Drugs Co-Administered with P antoprazole Sodium for Injection and Interaction with Diagnostics Antiretrovirals C linical Impact: The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known. • Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with pantoprazole may reduce antiviral effect and promote the development of drug resistance . • Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with pantoprazole may increase toxicity [see Clinical Pharmacology (12.3 )] . • There are other antiretroviral drugs which do not result in clinically relevant interactions with pantoprazole. I ntervention: R ilpivirine-containing products: Concomitant use with Pantoprazole Sodium for Injection is contraindicated [see Contraindications (4) ] . See prescribing information. Atazanavir: See prescribing information for atazanavir for dosing information. Nelfinavir: Avoid concomitant use with Pantoprazole Sodium for Injection. See prescribing information for nelfinavir. S a quinavir: See the prescribing information for saquinavir and for monitoring of potential saquinavir-related toxicities. Other antiretrovirals: See prescribing information for specific antiretroviral drugs. Warfarin C linical Impact: Increased INR and prothrombin time in patients receiving PPIs, including pantoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. I ntervention: Monitor INR and prothrombin time and adjust the dose of warfarin, if needed, to maintain the target INR range. See prescribing information for warfarin. Clopidogrel C linical Impact: Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel-induced platelet inhibition [see Clinical Pharmacology (12.3) ]. I ntervention: No dose adjustment of clopidogrel is necessary when administered with an approved dose of Pantoprazole Sodium for Injection. Met h otrexate C linical Impact: Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted [see Warnings and Precautions (5.13) ]. I ntervention: A temporary withdrawal of Pantoprazole Sodium for Injection may be considered in some patients receiving high-dose methotrexate. Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, n ilotinib, mycophenoloate mofetil, ketoconazole/itraconazole) C linical Impact: Pantoprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity I ntervention: Mycophenolate mofetil (MMF): Co-administration of pantoprazole sodium in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH [see Clinical Pharmacology (12.3 )] . The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving Pantoprazole Sodium for Injection and MMF. Use Pantoprazole Sodium for Injection with caution in transplant patients receiving MMF [see Clinical Pharmacology (12.3) ] . See the prescribing information for other drugs dependent on gastric pH for absorption. Interactions with Investigations of Neuroendocrine Tumors C linical Impact: CgA levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors [see Warnings and Precautions (5.11) , Clinical Pharmacology (12.2) ] . I ntervention: Temporarily stop Pantoprazole Sodium for Injection treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary. F alse Positive Urine Tests for THC C linical Impact: There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs, including pantoprazole sodium [see Warnings and Precautions (5.12 )] . I ntervention: An alternative confirmatory method should be considered to verify positive results. See full prescribing information for a list of clinically important drug interactions. ( 7 )
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